Study of XL114 in Subjects With Non-Hodgkin's Lymphoma

NCT05144347 | Terminated Phase 1 FDA Drug

• 1 other identifier: XL114-101
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1, non-randomized, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical antitumor activity of XL114 administered alone orally to subjects with Non-Hodgkin's Lymphoma (NHL). The objectives of the study also include determining the recommended dose (RD) and/or maximum tolerated dose (MTD) of XL114.

Conditions

Non-Hodgkin's Lymphoma (NHL); Activated B-Cell Type Diffuse Large B-Cell Lymphoma (ABC-DLBCL); Mantle Cell Lymphoma (MCL); Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

Mucosa-associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT-1); B-cell Malignancies; Fatty Acid Binding Protein 5 (FABP-5)

Outcome Measures

Primary Outcomes (2)

• Dose-Escalation Stage: Recommended Dose (RD) and/or Maximum Tolerated Dose (MTD) for XL114

  To determine the RD and/or MTD of XL114 administered orally in subjects with NHL

  4-6 months

• Cohort-Expansion Stage: Objective Response Rate (ORR)

  To evaluate preliminary efficacy of XL114 by estimating the ORR based on lymphoma-specific response criteria as assessed by the Investigator

  4-6 months

Secondary Outcomes (11)

• Safety of XL114, as evaluated by Adverse Events (AEs)

  4-6 months

• Tolerability of XL114, as evaluated by Dose Intensity, Dose Modifications, and Study Discontinuation due to AEs

  4-6 months

• Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)

  4-6 months

• Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)

  4-6 months

• Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)

  4-6 months

Study Arms (2)

XL114 Dose-Escalation Cohorts

EXPERIMENTAL

Subjects (Cohort A1-An) will accrue in cohorts of 3-12 subjects in a i3+3 design.

Drug: XL114

XL114 Expansion Cohorts

EXPERIMENTAL

The recommended dose from the Dose-Escalation stage, will be used in subjects with activated B-cell-like diffuse large B-cell lymphoma \[ABC-DLBCL\] (Cohort B), mantle cell lymphoma \[MCL\] (Cohort C), chronic lymphocytic leukemia \[CLL\]/small lymphocytic lymphoma \[SLL\] (Cohort D). Subjects will also be enrolled in a Biomarker cohort (Cohort E).

Drug: XL114

Interventions

XL114 DRUG

Tablets of XL114

XL114 Dose-Escalation Cohorts; XL114 Expansion Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose-Escalation Stage (Cohort A) and Cohort-Expansion Stage (B-E): The subject has received standard life-prolonging therapies or are not qualified to receive such therapies.

You may not qualify if:

• Cohort-Expansion Stage Cohort B (ABC-DLBCL subtype): Subjects with histologically documented activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) subtype. Note: De novo or transformed diffuse large B-cell lymphoma (DLBCL) from previously diagnosed indolent lymphoma (eg, follicular lymphoma) is allowed.
• Cohort-Expansion Stage Cohort C (MCL): Subjects with histologically documented MCL with monoclonal B-cells that show a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1.
• Cohort-Expansion Stage Cohort D (CLL/SLL): Subjects with histologically documented CLL/SLL per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.
• Cohort-Expansion Stage Cohort E, Biomarker Cohort (ABC-DLBCL, MCL, and SLL): Subjects with ABC-DLBCL, MCL, and SLL that fulfill the subject disease characteristics criteria as described for Cohorts B, C, or D.
• Cohort-Expansion Stage: Subjects with ABC-DLBCL, MCL, and SLL must have measurable disease by revised criteria for response assessment of lymphoma.
• Cohort-Expansion Stages: Must have archival tumor tissue available, which was collected up to 2 years prior to consent for this study. If archival tumor tissue is not available, a fresh tumor biopsy may be obtained (if safe to acquire) up to 60 days prior to first dose.
• Biomarker Cohort: Subjects must provide a fresh tumor biopsy up to 60 days prior to first dose, at week 2, day 1 (W2D1) after initiation of XL114, and at disease progression. Note: The tumor tissue requirement in the Expansion and Biomarker cohorts doesn't apply for subjects with CLL.
• Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 \[CTCAE v5\]) from AEs, unless AEs are clinically nonsignificant or stable.
• Left ventricular ejection fraction (LVEF) \> 50% as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan per local standard.
• Age 18 years or older on the day of consent.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
• Adequate organ and marrow function
• Sexually active fertile subjects and their partners must agree to highly effective methods of contraception.
• Female subjects of childbearing potential must not be pregnant at screening.
• Receipt of prior therapies as defined in the protocol

Sponsors & Collaborators

• Exelixis: lead

Study Sites (4)

Exelixis Clinical Site #3

Tucson, Arizona, 85719, United States

Location

Exelixis Clinical Site #1

Indianapolis, Indiana, 46250, United States

Location

Exelixis Clinical #4

Pittsburgh, Pennsylvania, 15224, United States

Location

Exelixis Clinical Site #2

Spokane, Washington, 99208, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose-escalation followed by Cohort-expansion in NHL-specific expansion cohorts

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: December 3, 2021
• Study Start: April 12, 2022
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: July 11, 2023

Record last verified: 2023-07

Locations

US (4)